Planar polarity and plasticity
Planar Cell Polarity (PCP) genes strongly affect neurulation, leading to a complete failure of neural tube closure and craniorachischisis, the most severe form of neural tube defects. This neurodevelopmental pathology is associated with massive structural disruption of the entire central nervous system and deficits in sensory systems, and is incompatible with life, preventing the study of potential roles of core PCP genes later in life. In our group, we want to understand the molecular and cellular mechanisms controlled by PCP signaling as well as the structural and functional consequences of their early (during embryonic development) or late (in adult) deletion, in correlation with specific subregions of the brain and in specific sensory organs (inner ear).
For this, we use classical molecular and cellular biology approaches and various types of imaging (from confocal, to light sheet microscopy to super-resolution, and live imaging), but also a variety of conditional mouse models (Cre-Lox), stereotaxic injections of viruses combined with complex behavioral protocols, electrophysiology, anatomical and immunohistological approaches.
Mots clés
ADHD (attention-deficit hyperactivity disorder), ASDs (Autism Spectrum Disorders), Adhésion cellulaire et cytosquelette, Apprentissage, Cognition, Comportement, Développement du système nerveux, Epilepsie, Imagerie cellulaire in vitro ou in vivo, Maladies Neuro-développementales, Maladies rares, Microscopie super-résolutive, Modèle génétique, Mémorisation des perceptions sensorielles, Plasticité synaptique, Retard mental, Signalisation, Synapse molecular complexes, Système auditif et d’équilibration, Trafic intracellulaire, Troubles de l’audition, Troubles du comportement, Ultrastructure neuronale et morphogénèseSelected publications
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The core PCP protein Prickle2 regulates axon number and AIS maturation by binding to AnkG and modulating microtubule bundling
Ana Dorrego-Rivas, Jerome Ezan, Maïté M. Moreau, Sonia Poirault-Chassac, Nathalie Aubailly, Julie De Neve, Camille Blanchard, Francis Castets, Amélie Fréal, Arne Battefeld, Nathalie Sans, Mireille Montcouquiol.
Sci. Adv.. 2022-09-09. 8 (36)
DOI: 10.1126/sciadv.abo6333 -
Neuron-Specific Deletion of Scrib in Mice Leads to Neuroanatomical and Locomotor Deficits
Jerome Ezan, Maité M. Moreau, Tamrat M. Mamo, Miki Shimbo, Maureen Decroo, Nathalie Sans, Mireille Montcouquiol.
Front. Genet.. 2022-05-25. 13
DOI: 10.3389/fgene.2022.872700 -
Early loss of Scribble affects cortical development, interhemispheric connectivity and psychomotor activity.
Jerome Ezan, Maité M. Moreau, Tamrat M. Mamo, Miki Shimbo, Maureen Decroo, Melanie Richter, Ronan Peyroutou, Rivka Rachel, Fadel Tissir, Froylan Calderon de Anda, Nathalie Sans, Mireille Montcouquiol.
Sci Rep. 2021-04-27. 11 (1)
DOI: 10.1038/s41598-021-88147-1 -
Muscle Van Gogh-like 2 shapes the neuromuscular synapse by regulating MuSK signaling activity
Myriam Boëx, Julien Messéant, Steve Cottin, Marius Halliez, Stéphanie Bauché, Céline Buon, Nathalie Sans, Mireille Montcouquiol, Jordi Molgó, Muriel Amar, Arnaud Ferry, Mégane Lemaitre, Andrée Rouche, Dominique Langui, Asha Baskaran, Bertrand Fontaine, Laure Strochlic.
Preprint bioRxiv. 2020-11-27.
DOI: 10.1101/2020.11.26.384925 -
Age-related impairment of declarative memory: linking memorization of temporal associations to GluN2B redistribution in dorsal CA1.
l Abed AS, Sellami A, Potier M, Ducourneau EG, Gerbeaud-Lassau P, Brayda-Bruno L, Lamothe V, Sans N, Desmedt A, Vanhoutte P, Bennetau-Pelissero C, Trifilieff P, Marighetto A..
Aging Cell. 2020 Oct 3. 19 (10) : e13243.
DOI: 10.1111/acel.13243 -
Vangl2 in the Dentate Network Modulates Pattern Separation and Pattern Completion
Benjamin J.A. Robert, Maïté M. Moreau, Steve Dos Santos Carvalho, Gael Barthet, Claudia Racca, Mehdi Bhouri, Anne Quiedeville, Maurice Garret, Bénédicte Atchama, Alice Shaam Al Abed, Christelle Guette, Deborah J. Henderson, Aline Desmedt, Christophe Mulle, Aline Marighetto, Mireille Montcouquiol, Nathalie Sans.
Cell Reports. 2020-06-01. 31 (10) : 107743.
DOI: 10.1016/j.celrep.2020.107743 -
Vangl2 acts at the interface between actin and N-cadherin to modulate mammalian neuronal outgrowth
Steve Dos-Santos Carvalho, Maite M Moreau, Yeri Esther Hien, Michael Garcia, Nathalie Aubailly, Deborah J Henderson, Vincent Studer, Nathalie Sans, Olivier Thoumine, Mireille Montcouquiol.
eLife. 2020-01-07. 9
DOI: 10.7554/eLife.51822 -
Selective neurodevelopmental and behavioral deficits in Scrib conditional knock-out mice recapitulate some phenotypes associated with the Verheij/8q23.4 deletion syndrome
Jerome Ezan, Maité M. Moreau, Tamrat M. Mamo, Miki Shimbo, Maureen Decroo, Melanie Richter, Ronan Peyroutou, Rivka Rachel, Fadel Tissir, Froylan Calderon de Anda, Nathalie Sans, Mireille Montcouquiol.
. 2019-09-23.
DOI: 10.1101/780130 -
Development and Patterning of the Cochlea: From Convergent Extension to Planar Polarity.
Mireille Montcouquiol, Matthew W. Kelley.
Cold Spring Harb Perspect Med. 2019-01-07. : a033266.
DOI: 10.1101/cshperspect.a033266 -
Gαi Proteins are Indispensable for Hearing.
Sandra Beer-Hammer, Sze Chim Lee, Stephanie A. Mauriac, Veronika Leiss, Isabel A. M. Groh, Ana Novakovic, Roland P. Piekorz, Kirsten Bucher, Chengfang Chen, Kun Ni, Wibke Singer, Csaba Harasztosi, Thomas Schimmang, Ulrike Zimmermann, Klaus Pfeffer, Lutz Birnbaumer, Andrew Forge, Mireille Montcouquiol, Marlies Knipper, Bernd Nürnberg, Lukas Rüttiger.
Cell Physiol Biochem. 2018-01-01. 47 (4) : 1509-1532.
DOI: 10.1159/000490867 -
Defective Gpsm2/Gαi3 signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome.
Stephanie A. Mauriac, Yeri E. Hien, Jonathan E. Bird, Steve Dos-Santos Carvalho, Ronan Peyroutou, Sze Chim Lee, Maite M. Moreau, Jean-Michel Blanc, Aysegul Geyser, Chantal Medina, Olivier Thoumine, Sandra Beer-Hammer, Thomas B. Friedman, Lukas Rüttiger, Andrew Forge, Bernd Nürnberg, Nathalie Sans, Mireille Montcouquiol.
Nat Comms. 2017-04-07. 8 : 14907.
DOI: 10.1038/ncomms14907 -
Activity-Dependent Neuroplasticity Induced by an Enriched Environment Reverses Cognitive Deficits in Scribble Deficient Mouse.
Muna L Hilal, Maité M Moreau, Claudia Racca, Vera L Pinheiro, Nicolas H Piguel, Marie-Josée Santoni, Steve Dos Santos Carvalho, Jean-Michel Blanc, Yah-Se K Abada, Ronan Peyroutou, Chantal Medina, Hélène Doat, Thomas Papouin, Laurent Vuillard, Jean-Paul Borg, Rivka Rachel, Aude Panatier, Mireille Montcouquiol, Stéphane H R Oliet, Nathalie Sans.
Cerebral Cortex. 2016-11-22. 27 (12) : 5635-5651.
DOI: 10.1093/cercor/bhw333 -
Planar Cell Polarity Gene Mutations in Autism Spectrum Disorder, Intellectual Disabilities, and Related Deletion/Duplication Syndromes
Nathalie Sans, Jérôme Ezan, Maïté M. Moreau, Mireille Montcouquiol.
Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability. 2016-01-01. : 189-219.
DOI: 10.1016/b978-0-12-800109-7.00013-3 -
Nutritional Omega-3 deficiency alters glucocorticoid receptor-signaling pathway and neuronal morphology in regionally distinct brain structures associated with emotional deficits
Thomas Larrieu, Muna L. Hilal, Véronique De Smedt-Peyrusse, Nathalie Sans, Sophie Layé.
Neural Plasticity. 2016-01-01. 2016 : 1-9.
DOI: 10.1155/2016/8574830 -
Microglial Activation Enhances Associative Taste Memory through Purinergic Modulation of Glutamatergic Neurotransmission
J.-C. Delpech, N. Saucisse, S. L. Parkes, C. Lacabanne, A. Aubert, F. Casenave, E. Coutureau, N. Sans, S. Laye, G. Ferreira, A. Nadjar.
Journal of Neuroscience. 2015-02-18. 35 (7) : 3022-3033.
DOI: 10.1523/jneurosci.3028-14.2015 -
The multiple links between cilia and planar cell polarity | Les liens multiples entre les cils et la polarité planaire cellulaire
Jérôme Ezan, Mireille Montcouquiol.
Med Sci (Paris). 2014-11-01. 30 (11) : 1004-1010.
DOI: 10.1051/medsci/20143011015 -
Scribble1/AP2 complex coordinates NMDA receptor endocytic recycling.
Nicolas H. Piguel, Sabine Fievre, Jean-Michel Blanc, Mario Carta, Maïté M. Moreau, Enora Moutin, Vera L. Pinheiro, Chantal Medina, Jerome Ezan, Léa Lasvaux, François Loll, Christelle M. Durand, Kai Chang, Ronald S. Petralia, Robert J. Wenthold, F. Anne Stephenson, Laurent Vuillard, Hervé Darbon, Julie Perroy, Christophe Mulle, Mireille Montcouquiol, Claudia Racca, Nathalie Sans.
Cell Reports. 2014-10-01. 9 (2) : 712-727.
DOI: 10.1016/j.celrep.2014.09.017 -
Nutritional omega-3 modulates neuronal morphology in the prefrontal cortex along with depression-related behaviour through corticosterone secretion.
T Larrieu, L M Hilal, C Fourrier, V De Smedt-Peyrusse, Sans N, L Capuron, S Layé.
Transl Psychiatry. 2014-10-01. 4 (10) : e468-e468.
DOI: 10.1038/tp.2014.108 -
A dual role for planar cell polarity genes in ciliated cells.
C. Boutin, P. Labedan, J. Dimidschstein, F. Richard, H. Cremer, P. Andre, Y. Yang, M. Montcouquiol, A. M. Goffinet, F. Tissir.
Proceedings of the National Academy of Sciences. 2014-07-14. 111 (30) : E3129-E3138.
DOI: 10.1073/pnas.1404988111 -
Primary cilium migration depends on G-protein signalling control of subapical cytoskeleton
Jerome Ezan, Léa Lasvaux, Aysegul Gezer, Ana Novakovic, Helen May-Simera, Edwige Belotti, Anne-Catherine Lhoumeau, Lutz Birnbaumer, Sandra Beer-Hammer, Jean-Paul Borg, André Le Bivic, Bernd Nürnberg, Nathalie Sans, Mireille Montcouquiol.
Nat Cell Biol. 2013-08-11. 15 (9) : 1107-1115.
DOI: 10.1038/ncb2819 -
Revisiting planar cell polarity in the inner ear
Jérôme Ezan, Mireille Montcouquiol.
Seminars in Cell & Developmental Biology. 2013-05-01. 24 (5) : 499-506.
DOI: 10.1016/j.semcdb.2013.03.012 -
Gipc1 has a dual role in Vangl2 trafficking and hair bundle integrity in the inner ear
A. P. Giese, J. Ezan, L. Wang, L. Lasvaux, F. Lembo, C. Mazzocco, E. Richard, J. Reboul, J.-P. Borg, M. W. Kelley, N. Sans, J. Brigande, M. Montcouquiol.
Development. 2012-09-18. 139 (20) : 3775-3785.
DOI: 10.1242/dev.074229 -
Dishevelled stabilization by the ciliopathy protein rpgrip1l is essential for planar cell polarity
Alexia Mahuzier, Helori-Mael Gaudé, Valentina Grampa, Isabelle Anselme, Flora Silbermann, Margot Leroux-Berger, Delphine Delacour, Jerome Ezan, Mireille Montcouquiol, Sophie Saunier, Sylvie Schneider-Maunoury, Christine Vesque.
J Cell Biol. 2012-08-27. 198 (5) : 927-940.
DOI: 10.1083/jcb.201111009 -
Down’s-syndrome-related kinase Dyrk1A modulates the p120-catenin-Kaiso trajectory of the Wnt signaling pathway
Ji Yeon Hong, Jae-Il Park, Moonsup Lee, William A. Muñoz, Rachel K. Miller, Hong Ji, Dongmin Gu, Jerome Ezan, Sergei Y. Sokol, Pierre D. McCrea.
J Cell Sci. 2012-06-15. 125 (12) : 3012-3012.
DOI: 10.1242/jcs.114710 -
SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism.
C M Durand, J Perroy, F Loll, D Perrais, L Fagni, T Bourgeron, M Montcouquiol, N Sans.
Mol Psychiatry. 2011-05-24. 17 (1) : 71-84.
DOI: 10.1038/mp.2011.57 -
The planar polarity protein Scribble1 is essential for neuronal plasticity and brain function.
M. M. Moreau, N. Piguel, T. Papouin, M. Koehl, C. M. Durand, M. E. Rubio, F. Loll, E. M. Richard, C. Mazzocco, C. Racca, S. H. R. Oliet, D. Nora Abrous, M. Montcouquiol, N. Sans.
Journal of Neuroscience. 2010-07-21. 30 (29) : 9738-9752.
DOI: 10.1523/jneurosci.6007-09.2010 -
Lack of cadherins Celsr2 and Celsr3 impairs ependymal ciliogenesis, leading to fatal hydrocephalus
Fadel Tissir, Yibo Qu, Mireille Montcouquiol, Libing Zhou, Kouji Komatsu, Dongbo Shi, Toshihiko Fujimori, Jason Labeau, Donatienne Tyteca, Pierre Courtoy, Yves Poumay, Tadashi Uemura, Andre M Goffinet.
Nat Neurosci. 2010-05-16. 13 (6) : 700-707.
DOI: 10.1038/nn.2555 -
Coupling between hydrodynamic forces and planar cell polarity orients mammalian motile cilia
Boris Guirao, Alice Meunier, Stéphane Mortaud, Andrea Aguilar, Jean-Marc Corsi, Laetitia Strehl, Yuki Hirota, Angélique Desoeuvre, Camille Boutin, Young-Goo Han, Zaman Mirzadeh, Harold Cremer, Mireille Montcouquiol, Kazunobu Sawamoto, Nathalie Spassky.
Nat Cell Biol. 2010-05-01. 12 (5) : 520-520.
DOI: 10.1038/ncb0510-520a -
Planar cell polarity defects and defective Vangl2 trafficking in mutants for the COPII gene Sec24b.
C. Wansleeben, H. Feitsma, M. Montcouquiol, C. Kroon, E. Cuppen, F. Meijlink.
Development. 2010-03-09. 137 (7) : 1067-1073.
DOI: 10.1242/dev.041434 -
Scrib regulates PAK activity during the cell migration process.
Sébastien Nola, Michael Sebbagh, Sylvie Marchetto, Naël Osmani, Claire Nourry, Stéphane Audebert, Christel Navarro, Rivka Rachel, Mireille Montcouquiol, Nathalie Sans, Sandrine Etienne-Manneville, Jean-Paul Borg, Marie-Josée Santoni.
Human Molecular Genetics. 2008-08-20. 17 (22) : 3552-3565.
DOI: 10.1093/hmg/ddn248 -
Detection of Planar Polarity Proteins in Mammalian Cochlea
Mireille Montcouquiol, Jennifer M. Jones, Nathalie Sans.
Methods in Molecular Biology. 2008-01-01. : 207-219.
DOI: 10.1007/978-1-59745-249-6_16 -
Proliferative responses to growth factors decline rapidly during postnatal maturation of mammalian hair cell epithelia
Rende Gu, Mireille Montcouquiol, Mark Marchionni, Jeffrey T. Corwin.
European Journal of Neuroscience. 2007-04-05. 25 (5) : 1363-1372.
DOI: 10.1111/j.1460-9568.2007.05414.x -
Polarité planaire chez les Mammifères : similitudes et divergences avec la Drosophile
Mireille Montcouquiol.
J. Soc. Biol.. 2007-01-01. 201 (1) : 61-68.
DOI: 10.1051/jbio:2007007 -
Noncanonical Wnt signaling and neural polarity.
Mireille Montcouquiol, E. Bryan Crenshaw, Matthew W. Kelley.
Annu. Rev. Neurosci.. 2006-07-21. 29 (1) : 363-386.
DOI: 10.1146/annurev.neuro.29.051605.112933 -
Asymmetric Localization of Vangl2 and Fz3 Indicate Novel Mechanisms for Planar Cell Polarity in Mammals
Montcouquiol M, Sans N, Huss D, Kach J, Dickman JD, Forge A, Rachel RA, Copeland NG, Jenkins NA, Bogani D, Murdoch J, Warchol ME, Wenthold RJ, Kelley MW..
Journal of Neuroscience. 2006-05-10. 26 (19) : 5265-5275.
DOI: 10.1523/jneurosci.4680-05.2006 -
Math1 regulates development of the sensory epithelium in the mammalian cochlea.
Chad Woods, Mireille Montcouquiol, Matthew W Kelley.
Nat Neurosci. 2004-11-07. 7 (12) : 1310-1318.
DOI: 10.1038/nn1349 -
Transcription profiling of inner ears from Pou4f3(ddl/ddl) identifies Gfi1 as a target of the Pou4f3 deafness gene.
Ronna Hertzano, Mireille Montcouquiol, Sharon Rashi-Elkeles, Rani Elkon, Raif Yücel, Wayne N. Frankel, Gideon Rechavi, Tarik Möröy, Thomas B. Friedman, Matthew W. Kelley, Karen B. Avraham.
Human Molecular Genetics. 2004-07-14. 13 (18) : 2143-2153.
DOI: 10.1093/hmg/ddh218 -
Wnt signaling mediates reorientation of outer hair cell stereociliary bundles in the mammalian cochlea.
Alain Dabdoub, Maura J. Donohue, Angela Brennan, Vladimir Wolf, Mireille Montcouquiol, David A. Sassoon, Jen-Chih Hseih, Jeffrey S. Rubin, Patricia C. Salinas, Matthew W. Kelley.
Development. 2003-06-01. 130 (11) : 2375-2384.
DOI: 10.1242/dev.00448 -
Identification of Vangl2 and Scrb1 as planar polarity genes in mammals.
Mireille Montcouquiol, Rivka A. Rachel, Pamela J. Lanford, Neal G. Copeland, Nancy A. Jenkins, Matthew W. Kelley.
Nature. 2003-04-30. 423 (6936) : 173-177.
DOI: 10.1038/nature01618
Team member(s)
Chercheurs, Praticiens hospitaliers...
Ingénieur(e)s, technicien(ne)s
Nathalie Aubailly Aubailly
Sonia Poirault-Chassac Poirault-Chassac
Charlotte Isch Isch
Lili Cluzel-Burgalat Cluzel-Burgalat
Amandine Martin Martin
Post-doctorant(s)
Doctorant(s)
Neuropsychologist(s) and speech therapist(s)
Ingénieur(s) hospitalier(s) et ARC